2-Hydroxy-N,N-dimethyl-3-[[2-[[1(R)-(5-methyl-2-furanyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]benzamide (compound of formula I):
is disclosed in U.S. application Ser. Nos. 10/122,841 (filed Apr. 15, 2002 and now abandoned), Ser. No. 10/208,412 (filed Jul. 30, 2002), and Ser. No. 10/241,326 (filed Sep. 11, 2002), the disclosures of each being incorporated herein by reference thereto. The compound of formula I is also disclosed in WO 02/083624 (filed Apr. 15, 2002 and published Oct. 24, 2002).
The compound of formula I is useful for treating CXC chemokine-mediated diseases. Chemokines are chemotactic cytokines that are released by a wide variety of cells to attract macrophages, T-cells, eosinophils, basophils, neutrophils and endothelial cells to sites of inflammation and tumor growth. The CXC-chemokines include interleukin-8 (IL-8), neutrophil-activating protein-1 (NAP-1), neutrophil-activating protein-2 (NAP-2), GROα, GROβ, GROγ, ENA-78, GCP-2, IP-10, MIG and PF4.
There remains a need for compounds that are capable of modulating activity at CXC-chemokine receptors. For example, conditions associated with an increase in IL-8 production (which is responsible for chemotaxis of neutrophil and T-cell subsets into the inflammatory site and growth of tumors) would benefit by compounds that are inhibitors of IL-8 receptor binding.
In view of the importance of antagonists that bind to the CXC-chemokine receptor novel methods of making such antagonists are always of interest.